1,4-Diazepane-2-ones as novel inhibitors of LFA-1

Bioorg Med Chem Lett. 2003 Feb 10;13(3):499-502. doi: 10.1016/s0960-894x(02)00991-5.

Abstract

The design, synthesis, and biological evaluation of 1,4-diazepane-2-ones as novel LFA-1 antagonists from a scaffold-based combinatorial library are described. Initial optimization of the library lead has resulted in high-affinity antagonists of the LFA-1/ICAM-1 interaction, such as compounds 18d and 18e with IC(50) values of 110 and 70 nM, respectively.

MeSH terms

  • Cell-Free System
  • Combinatorial Chemistry Techniques
  • Crystallography, X-Ray
  • Drug Design
  • Heterocyclic Compounds, 1-Ring / chemical synthesis*
  • Heterocyclic Compounds, 1-Ring / pharmacology*
  • Indicators and Reagents
  • Intercellular Adhesion Molecule-1 / drug effects*
  • Lymphocyte Function-Associated Antigen-1 / drug effects*
  • Models, Molecular
  • Molecular Conformation
  • Structure-Activity Relationship

Substances

  • Heterocyclic Compounds, 1-Ring
  • Indicators and Reagents
  • Lymphocyte Function-Associated Antigen-1
  • Intercellular Adhesion Molecule-1